Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Investigation shows multi-antiviral-resistant H1N1 flu

A case report on an immunocompromised patient with prolonged influenza virus in yesterday's Eurosurveillance reveals resistance to two common antiviral drugs and shows how rapidly antiviral resistance can evolve, a finding the authors say highlights the importance of rapid antiviral resistance testing.

The report involved a Danish man with chronic lymphocytic leukemia who had prolonged shedding of 2009 H1N1 influenza A virus for 6 months and was treated with the antivirals oseltamivir (Tamiflu) and zanamivir (Relenza). Investigation of respiratory samples using Sanger sequencing and next-generation sequencing showed that resistance to oseltamivir, caused by resistance mutation H275Y, was detected 15 days after the end of the first treatment with the antiviral and likely limited the effect of the second treatment.

On day 96 of the treatment, 1 week after the patient had begun inhalation therapy with zanamivir and 3 months after onset of symptoms, respiratory samples contained virus with the H275Y mutation and an additional S247N mutation. By day 149, when the patient had almost completed the second zanamivir treatment, genetic sequencing detected the H257Y, I233R, and E119G mutations, along with two additional mutations, showing a more complex viral population in the patient and resistance to zanamivir as well as oseltamivir.

"The rapidly evolving antiviral resistance observed in this case," the authors write, "emphasises the importance of timely antiviral resistance testing during treatment of influenza virus infection in order to change treatment regime and avoid unnecessary administration of ineffective medicaments, as well as preventing spread of antiviral resistant viruses."
Jan 19 Eurosurveill research article

Fecal transplant via enema found to be most cost effective for C diff

A French analysis of five different strategies for the treatment of recurrent Clostridium difficileinfection (CDI) indicates that fecal microbiota transplantation (FMT) via enema is the most cost effective, according to a study yesterday in PLoS One.

CDI is the leading cause of healthcare-associated diarrhea, and incidence and severity have been on the rise in North America and Europe in recent years.  Recurrent infections are also a problem, the authors of the study explain, with the risk of recurrent CDI in patients who have already had one recurrence rising from 25% after an initial episode to 45% after a first recurrence and to 65% after two recurrences.

Using a decision-analytic simulation model, the French researchers set out to compare five treatments for the management of second recurrence of community-onset CDI: (1) pulse-tapered vancomycin (the current standard approach), (2) fidaxomicin, (3) FMT via colonoscopy, (4) FMT via duodenal infusion, (5) and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), and ICERs were interpreted using a willingness-to-pay threshold of €32,000/QALY ($34,226/QALY).

The decision model indicated that while pulse-tapered vancomycin was less costly than FMT, FMT in all modes of delivery was more effective. FMT via colonoscopy and FMT via enema were both more effective than pulse-tapered vancomycin, but FMT via enema was the less expensive option. The extra cost for FMT via enema for increased effectiveness compared with vancomycin was €18,092/QALY ($19,356/QALY), while the extra cost for FMT via colonoscopy compared with FMT via enema was €73,653/QALY ($78,798/QALY).

"Thus, FMT via enema appears to be the most cost-effective strategy at a willingness to pay threshold of €32,000/QALY," the authors write.
Jan 19 PLoS One study 

Revised sepsis guidelines include antibiotic prescribing, optimization
Originally published by CIDRAP News Jan 19

A fourth revision of international guidelines for managing sepsis and septic shock, published today in JAMA, includes several updates on antibiotic prescribing, including a recommendation for quick control of source infections.

The guidelines, first published in 2004 and revised in 2008 and 2012, are from the Surviving Sepsis Campaign, Society of Critical Care Medicine, and European Society of Intensive Care Medicine.

In emphasizing rapid source-infection control, the guidelines recommend instituting broad-spectrum intravenous antibiotics as soon as possible and within an hour surgery or  a procedure, such as the retrieval of a catheter suspected to be infected. The step is recommended because any delay has been tied to an increased risk of death. The guidelines also advise using antibiotic dosing strategies based on pharmacokinetics and pharmacodynamics principles when such tests are available, because initial doses for sepsis cases are often too low.

The authors of the guidance, which was developed with the input of 55 international experts, provide a "weak recommendation" (meaning not as strongly backed by evidence) for the use of empirical combination antibiotic therapy in patients with septic shock, but not for sepsis without shock. The reason for using antibiotics from two different classes in this situation would be to address the increased frequency of antimicrobial-resistant pathogens.

To optimize stewardship, the guidance says to assess patients daily for de-escalation of antimicrobials and to narrow therapy based on cultures, clinical improvement, or both.

Sepsis occurs when the body's infection-fighting response causes life-threatening organ dysfunction. It is a leading cause of death, morbidity, and expense and contributes to one third to a half of deaths of hospitalized patients, the authors write.
Jan 19 JAMA guidelines
Jan 19 JAMA commentary on the guidelines

Studies indicate antimicrobial-coated sutures reduce surgical infections

Originally published by CIDRAP News Jan 18

Two new papers in the British Journal of Surgery found that antimicrobial-coated sutures are effective at reducing surgical-site infections (SSIs) and could produce substantial cost savings.

In one paper, a meta-analysis of 21 randomized clinical trials involving 6,462 patients that were conducted from 1990 through 2015, investigators found that the use of sutures coated with triclosan, when compared with uncoated sutures, reduced the risk of SSIs by 15%, cutting the number of SSIs per 1,000 procedures by 39.

In the other paper, an economic meta-analysis of 34 randomized trials published from 2005 through 2016, investigators found that using antimicrobial sutures produced a mean savings of £91.25 ($111.92) per surgical procedure across all wound classes compared with sutures without the coating.

"Antimicrobial sutures ought to be included into SSI care bundles and provide a further significant saving to National Health Service (England) surgical practice," David Leaper, MD, ChM, lead author of the economic analysis, said in a press release from journal publisher Wiley.

The US Centers for Disease Control and Prevention (CDC) estimates that there were 157,500 SSIs from any inpatient surgery in the United States in 2011, the most recent year for which data are available. Preventing SSIs from occurring is seen as a critical part of efforts to reduce the use of antibiotics.
Jan 17 Br J Surg study
Jan 17 Br J Surg economic study
Jan 17 Wiley press release 

UV-light disinfection might cut hospital MRSA, VRE rates

Originally published by CIDRAP News Jan 17

An expensive type of ultraviolet (UV) light treatment called UVC was associated with a 30% drop in the incidence of infections with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) but did not affect Clostridium difficile rates when used for cleaning hospital rooms between patients, according to a study yesterday in The Lancet.

The study, conducted by Duke Health researchers and funded by the US Centers for Disease Control and Prevention, was conducted from 2012 to 2014 at nine hospitals in the Southeast, including three Duke University Health System hospitals, a Veterans Affairs hospital, and small community facilities. It included 21,393 patients.

The hospitals used a portable UVC machine to disinfect rooms where patients with the target bacteria had been staying. For about 30 minutes, the device emits UVC light into an empty room and kills bacteria by disrupting their DNA.

The trial compared standard disinfection with quaternary ammonium to three other cleaning methods: using quaternary ammonium followed by UV light, applying chlorine bleach instead of quaternary ammonium and no UV light, and cleaning with bleach and UV light.

Overall, the most effective strategy was using quaternary ammonium followed by UV light, which was particularly effective against MRSA. Using chlorine bleach instead of quaternary ammonium cut VRE by more than half, and adding UV light to the bleach regimen was even more successful, cutting VRE transmission 64%. Adding UV light did not change the C difficile rate for any method.

"Some of these germs can live on the environment so long that even after a patient with the organism has left the room and it has been cleaned, the next patient in the room could potentially be exposed," said Deverick J. Anderson, MD, an infectious disease specialist at Duke Health and lead investigator, in a Duke University news release. "Infections from one of these bugs are tough and expensive to treat and can be truly debilitating for a patient. For hospitals, these infections also cause a burden of costs that often aren't reimbursable."

In a Lancet commentary, experts from Methodist Dallas Medical Center, who weren't involved in the study, wrote, "These results are welcome at a time of crucial action in combatting resistant microbes. . . . Further investigation of the role of UV light in preventing C difficile infection, including multiple cycles and bathroom disinfection, is warranted to decipher the lack of clinical effect for this key pathogen."

Potential detriments include the price tag of the UVC unit, which can be as high as $90,000, and the relatively long disinfection time. Larger hospitals, which might turn over 100 patient beds in a day, might not be able to spare an extra half hour for room cleaning, Anderson said.
Jan 16 Lancet study
Jan 16 Lancet commentary
Jan 16 Duke University news release

Study finds high colonization rates of drug-resistant pathogens in refugees

Originally published by CIDRAP News Jan 17

A new study suggests that refugees seeking asylum in Europe may be bringing with them higher carriage rates of antibiotic-resistant bacteria.

In the observational study, published in PLoS One, 261 refugees at four refugee centers in Switzerland were screened to determine colonization rates for MRSA and extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae. Pharyngeal, nasal, and inguinal swabs were used for MRSA screening, and rectal swabs and urine were used for ESBL and carbapenemase screening.

The refugees were from five different regions—Middle East, East Africa, Central/West Africa, Northern Africa, and Far East—with the majority coming from Afghanistan, Syria, and Eritrea. Three quarters of the screening participants were male.

The screening results showed that 15.7% of the refugees were colonized with MRSA, a rate roughly 10 times higher than found in the Swiss population. But the rate of colonization ranged widely between the four refugee centers, with one particular center showing a colonization rate of 25.4%. The study authors determined, through the use of whole-genome sequencing, that this was likely due to a large outbreak in that camp and a series of smaller transmission events. The authors suggest that the living conditions in the refugee centers could facilitate MRSA transmission.

The ESBL colonization rate among the refugees was 23.7%, about 2 to 5 times higher compared to the Swiss population, with significantly higher colonization in persons originating from the Middle East. All the ESBL strains were Escherichia coli. Because no EBL isolates were available for whole-genome sequencing, it could not be determined if person-to-person transmission within a refugee center was taking place, as was the case with MRSA. No carbapenemase-producing isolates were identified.

"In summary, our data suggests, that for all refugees admitted to medical care facilities in Europe, screening and potentially contact isolation should be performed," the authors write.
Jan 13 PLoS One study